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Two spurge species, Euphorbia resinifera O. Berg and Euphorbia officinarum subsp. echinus (Hook.f. & Coss.) Vindt inhibit colon cancer 两种刺玫--Euphorbia resinifera O. Berg 和 Euphorbia officinarum subsp.
2区 医学 Q1 Medicine Pub Date : 2024-07-10 DOI: 10.1186/s12906-024-04566-3
Rania Benjamaa, Anlin Zhu, Soeun Kim, Dohyang Kim, Abdel Khalid Essamadi, Abdelkarim Moujanni, Anass Terrab, Namki Cho, Jaewoo Hong
Colon cancer, a prominent contributor to global cancer-related deaths, prompts the need for innovative treatment strategies. Euphorbia resinifera O. Berg (E. resinifera) and Euphorbia officinarum subsp. echinus Hook. f. & Coss Vindt (E. echinus) and their bee-derived products have been integral to traditional Moroccan medicine due to their potential health benefits. These plants have historical use in addressing various health issues, including cancer. However, their effects against colon cancer remain unclear, and the specific mechanisms underlying their anti-cancer effects lack comprehensive investigation. The study aimed to assess the potential anti-cancer effects of Euphorbia extract on colon cancer cell lines (DLD-1) through various techniques. The apoptosis, migration, and proliferation of DLD-1 cells were measured in DLD-1 cells. In addition, we conducted High-Performance Liquid Chromatography (HPLC) analysis to identify the profile of phenolic compounds present in the studied extracts. The extracts demonstrated inhibition of colon cancer cell migration. E. resinifera flower and E. echinus stem extracts show significant anti-migratory effects. Regarding anti-proliferative activity, E. resinifera flower extract hindered proliferation, whereas E. echinus flower extract exhibited dose-dependent inhibition. Apoptosis assays revealed E. resinifera flower extract inducing early-stage apoptosis and E. echinus flower extract promoting late-stage apoptosis. While apoptotic protein expression indicated, E. resinifera stem and propolis extracts had minimal impact on apoptosis. The findings provide evidence supporting the beneficial effects of E resinifera and E. echinus extracts on colon cancer and exerting anti-cancer properties.
结肠癌是导致全球癌症相关死亡的主要原因之一,因此需要创新的治疗策略。Euphorbia resinifera O. Berg(E. resinifera)和 Euphorbia officinarum subsp.这些植物在解决包括癌症在内的各种健康问题方面有着悠久的历史。然而,它们对结肠癌的作用仍不明确,其抗癌作用的具体机制也缺乏全面的研究。本研究旨在通过各种技术评估大戟提取物对结肠癌细胞株(DLD-1)的潜在抗癌作用。我们测定了 DLD-1 细胞的凋亡、迁移和增殖。此外,我们还进行了高效液相色谱(HPLC)分析,以确定所研究提取物中存在的酚类化合物的概况。这些提取物都具有抑制结肠癌细胞迁移的作用。E.resinifera花和E.echinus茎提取物具有显著的抗迁移作用。在抗增殖活性方面,E. resinifera 花提取物阻碍了细胞的增殖,而 E. echinus 花提取物则表现出剂量依赖性抑制作用。细胞凋亡试验表明,树脂花提取物可诱导早期细胞凋亡,而刺五加花提取物则可促进晚期细胞凋亡。凋亡蛋白的表达表明,树脂草茎提取物和蜂胶提取物对细胞凋亡的影响很小。这些研究结果为树脂草和刺五加提取物对结肠癌的有益影响和抗癌特性提供了证据。
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引用次数: 0
Bioactivity and antibacterial effect of star anise biosynthesized silver nanoparticles against Streptococcus mutans: an in vitro study 八角生物合成银纳米粒子对变异链球菌的生物活性和抗菌效果:体外研究
2区 医学 Q1 Medicine Pub Date : 2024-07-10 DOI: 10.1186/s12906-024-04550-x
Marwa Aly Elchaghaby, Sayed Rashad, Nada Mohamed Wassef
Silver nanoparticles (AgNPs) are receiving a lot of attention as a prospective antibacterial agent for use in caries prevention. The objective of this study was to investigate the bioactivity and antibacterial effect of silver nanoparticles biosynthesized using Star Anise against Streptococcus mutans (S.mutans). The bioactive components of the Star Anise were assessed by employing the gas chromatography-mass spectrometry technique. The antibacterial activities of Star Anise Biosynthesized Silver Nanoparticles against S.mutans bacteria were evaluated using Bauer and Kirby’s disc diffusion mechanism and the minimum inhibitory concentration. Silver nanoparticles biosynthesized using Star Anise revealed high antioxidant activity. AgNPs inhibited S. mutans with a 16 mm inhibition zone diameter and demonstrated an 80 µg/ml minimum inhibitory concentration. Biologically synthesized AgNPs made from aqueous extract of Star anise appear to be a potential and effective bactericidal agent against S.mutans that can be used to prevent dental caries.
银纳米粒子(AgNPs)作为一种可用于预防龋齿的抗菌剂,正受到广泛关注。本研究的目的是调查使用八角茴香生物合成的银纳米粒子对变异链球菌(S.mutans)的生物活性和抗菌效果。研究采用气相色谱-质谱联用技术对八角中的生物活性成分进行了评估。使用鲍尔和柯比的盘扩散机制和最小抑菌浓度评估了八角生物合成银纳米粒子对变异链球菌的抗菌活性。使用八角茴香生物合成的银纳米粒子具有很高的抗氧化活性。AgNPs 可抑制变形杆菌,抑制区直径为 16 毫米,最低抑制浓度为 80 微克/毫升。由八角水提取物生物合成的 AgNPs 似乎是一种潜在而有效的杀菌剂,可用于预防龋齿。
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引用次数: 0
Seagrass as a potential nutraceutical to decrease pro-inflammatory markers 海草是一种潜在的营养保健品,可减少促炎标记物
2区 医学 Q1 Medicine Pub Date : 2024-07-10 DOI: 10.1186/s12906-024-04532-z
Vani Mathakala, Tejaswini Ullakula, Uma Maheswari Devi Palempalli
The Pro-inflammatory mediators such as prostaglandin E2, nitric oxide and TNF-α are the key players in the stimulation of the inflammatory responses. Thus, the pro-inflammatory mediators are considered to be potential targets for screening nutraceutical with anti-inflammatory activity. In this context, we explored the anti-inflammatory potency of seagrass extract with western blot (Bio-Rad) analysis by using LPS induced RAW macrophages as in-vitro models, western blot analysis, In-silico methods using Mastero 13.0 software. The anti-inflammatory activity of Seagrass was demonstrated through down regulation of Pro-inflammatory markers such as Cyclooxygenase-2, induced Nitric oxide synthase and prostaglandin E synthase-1. The results were validated by docking the phytochemical constituents of seagrass namely Isocoumarin, Hexadecanoic acid, and Cis-9 Octadecenoic acid, 1,2 Benzene dicarboxylic acid and beta-sitosterol with TNF-alpha, COX-2, iNOS and PGES-1. The methanolic extract of seagrass Halophila beccarii is a potential nutraceutical agent for combating against inflammation with a significant anti-inflammatory activity.
前列腺素 E2、一氧化氮和 TNF-α 等促炎介质是刺激炎症反应的关键因素。因此,促炎介质被认为是筛选具有抗炎活性的营养保健品的潜在目标。在此背景下,我们以 LPS 诱导的 RAW 巨噬细胞为体外模型,通过 Western 印迹(Bio-Rad)分析、Western 印迹分析和使用 Mastero 13.0 软件的 In-silico 方法探讨了海草提取物的抗炎功效。海草的抗炎活性是通过对环氧合酶-2、诱导一氧化氮合酶和前列腺素 E 合酶-1 等促炎标志物的下调来体现的。通过将海草的植物化学成分(异香豆素、十六烷酸、顺-9 十八烯酸、1,2 苯二甲酸和 beta-谷甾醇)与 TNF-α、COX-2、iNOS 和 PGES-1 进行对接,验证了上述结果。海草甲醇提取物具有显著的抗炎活性,是一种潜在的抗炎营养保健品。
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引用次数: 0
Pasteurized form of a potential probiotic lactobacillus brevis IBRC-M10790 exerts anti-inflammatory effects on inflammatory bowel disease in vitro 潜在益生菌乳酸杆菌 IBRC-M10790 的巴氏杀菌型在体外对炎症性肠病具有抗炎作用
2区 医学 Q1 Medicine Pub Date : 2024-07-10 DOI: 10.1186/s12906-024-04576-1
Ardeshir Ebrahiminejad, Abbas Akhavan Sepahi, Abbas Yadegar, Anna Meyfour
Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal system. So far, no treatment has been identified that can completely cure IBD. Lactobacillus brevis is hypothesized to be beneficial in preventing inflammation. This study aimed to evaluate the potential probiotic effects of live and pasteurized L. brevis IBRC-M10790 on the in vitro cell co-culture model of IBD. An in vitro intestinal model was established using a transwell co-culture system of Caco-2 intestinal epithelial cells and RAW264.7 macrophages. Inflammatory conditions were induced in RAW264.7 cells using lipopolysaccharide. The effects of live and pasteurized L. brevis IBRC-M10790 on inflammatory mediators and epithelial barrier markers were investigated. L. brevis IBRC-M10790 was able to significantly decrease the proinflammatory cytokines (IL-6, IL-1β, and TNF-α) and increase the anti-inflammatory cytokine (IL-10) in the in vitro co-culture system. In addition, L. brevis increased adherens and tight junction (TJ) markers (ZO-1, E-cadherin, and Occludin) in Caco-2 intestinal epithelial cells. Based on the results, pasteurized L. brevis showed a higher protective effect than live L. brevis. Our findings suggest that live and pasteurized forms of L. brevis possess probiotic properties and can mitigate inflammatory conditions in IBD.
炎症性肠病(IBD)是一种慢性、复发性胃肠系统炎症性疾病。迄今为止,还没有找到能够彻底治愈 IBD 的治疗方法。据推测,乳酸杆菌对预防炎症有益。本研究旨在评估活的和巴氏杀菌的布氏乳杆菌 IBRC-M10790 对 IBD 体外细胞共培养模型的潜在益生作用。利用 Caco-2 肠上皮细胞和 RAW264.7 巨噬细胞的 Transwell 共培养系统建立了体外肠道模型。利用脂多糖诱导 RAW264.7 细胞产生炎症。研究了活的和巴氏杀菌的 L. brevis IBRC-M10790 对炎症介质和上皮屏障标志物的影响。在体外共培养系统中,L. brevis IBRC-M10790 能显著降低促炎细胞因子(IL-6、IL-1β 和 TNF-α),增加抗炎细胞因子(IL-10)。此外,L. brevis 还能增加 Caco-2 肠上皮细胞中的粘连和紧密连接(TJ)标记物(ZO-1、E-cadherin 和 Occludin)。结果表明,巴氏杀菌法的乳头酵母菌比活的乳头酵母菌具有更高的保护作用。我们的研究结果表明,活体和巴氏杀菌型布莱维氏菌具有益生菌特性,可减轻 IBD 的炎症状况。
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引用次数: 0
A systematic review of sham acupuncture validation studies 假针灸验证研究的系统回顾
2区 医学 Q1 Medicine Pub Date : 2024-06-05 DOI: 10.1186/s12906-024-04506-1
Sung Min Lim, Eunji Go
Acupuncture is widely used worldwide; however, studies on its effectiveness have been impeded by limitations regarding the design of appropriate control groups. In clinical research, noninvasive sham acupuncture techniques can only be applied through validation studies. Therefore, this systematic review aimed to evaluate the scope of existing literature on this topic to identify trends. We queried Pubmed, EMBASE, and the Cochrane Central Register of Controlled Trials databases from inception to July 2022 for relevant articles. Author names were used to identify additional relevant articles. Two independent reviewers assessed the identified articles based on the inclusion and exclusion criteria. The following data were extracted: study design, information regarding acupuncturists and participants, general and treatment-related characteristics of the intervention and control groups, participants’ experience of acupuncture, and research findings. The database query yielded 673 articles, of which 29 articles were included in the final review. Among these, 18 involved the use of one of three devices: Streitberger (n = 5), Park (n = 7), and Takakura (n = 6) devices. The remaining 11 studies used other devices, including self-developed needles. All the included studies were randomized controlled trials. The methodological details of the included studies were heterogeneous with respect to outcomes assessed, blinding, and results. Sham acupuncture validation studies have been conducted using healthy volunteers, with a focus on blind review and technological developments in sham acupuncture devices. However, theren may be language bias in our findings since we could not query Chinese and Japanese databases due to language barriers. There is a need for more efforts toward establishing control groups suitable for various acupuncture therapy interventions. Moreover, there is a need for more rigorous sham acupuncture validation studies, which could lead to higher-quality clinical studies.
针灸在世界范围内被广泛使用,然而,对其有效性的研究却受到了设计适当对照组的限制。在临床研究中,非侵入性假针灸技术只能通过验证研究来应用。因此,本系统性综述旨在评估有关该主题的现有文献范围,以确定趋势。我们在 Pubmed、EMBASE 和 Cochrane Central Register of Controlled Trials 数据库中查询了从开始到 2022 年 7 月的相关文章。我们还利用作者姓名确定了其他相关文章。两位独立审稿人根据纳入和排除标准对确定的文章进行了评估。提取的数据包括:研究设计、针灸师和参与者的相关信息、干预组和对照组的一般特征和治疗相关特征、参与者的针灸经验以及研究结果。通过数据库查询获得了 673 篇文章,其中 29 篇文章被纳入最终综述。其中,18 篇涉及三种设备之一的使用:Streitberger(5 篇)、Park(7 篇)和 Takakura(6 篇)装置。其余 11 项研究使用了其他装置,包括自行开发的针头。所有纳入的研究均为随机对照试验。纳入研究的方法细节在评估结果、盲法和结果方面存在差异。假针灸验证研究一直使用健康志愿者进行,重点关注盲法审查和假针灸设备的技术发展。然而,由于语言障碍,我们无法查询中文和日文数据库,因此我们的研究结果可能存在语言偏差。我们需要做出更多努力,建立适合各种针灸疗法干预的对照组。此外,还需要进行更严格的假针灸验证研究,从而开展更高质量的临床研究。
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引用次数: 0
Medical ethnobotany 医学人种植物学
2区 医学 Q1 Medicine Pub Date : 2024-06-05 DOI: 10.1186/s12906-024-04515-0
Adeyemi O. Aremu, Binsheng Luo, Sakina Mussarat
This collection on medical ethnobotany focuses on contributions that explore the invaluable potential associated with the ethnobotanical uses of medicinal plants, their phytochemical profiling, safety, and efficacy studies as well as their cultural and ecological context. This call for papers is expected to expand the knowledge base on how medicinal plants contribute toward the achievement of the United Nations Sustainable Development Goals (UN SDGs), in this case, goal 15 (life on land).
这本关于药用民族植物学的论文集侧重于探讨与药用植物的民族植物学用途、植物化学成分分析、安全性和功效研究及其文化和生态背景相关的宝贵潜力。本次征文活动有望扩大知识库,了解药用植物如何为实现联合国可持续发展目标(UN SDGs)做出贡献,这里指的是目标 15(陆地生命)。
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引用次数: 0
Mechanistic prediction and validation of Brevilin A Therapeutic effects in Lung Cancer Brevilin A 对肺癌治疗效果的机制预测与验证
2区 医学 Q1 Medicine Pub Date : 2024-06-05 DOI: 10.1186/s12906-024-04516-z
Ruixue Wang, Cuiyun Gao, Meng Yu, Jialing Song, Zhenzhen Feng, Ruyu Wang, Huafeng Pan, Haimeng Liu, Wei Li, Xiangzhen Fan
Traditional Chinese medicine (TCM) has been found widespread application in neoplasm treatment, yielding promising therapeutic candidates. Previous studies have revealed the anti-cancer properties of Brevilin A, a naturally occurring sesquiterpene lactone derived from Centipeda minima (L.) A.Br. (C. minima), a TCM herb, specifically against lung cancer. However, the underlying mechanisms of its effects remain elusive. This study employs network pharmacology and experimental analyses to unravel the molecular mechanisms of Brevilin A in lung cancer. The Batman-TCM, Swiss Target Prediction, Pharmmapper, SuperPred, and BindingDB databases were screened to identify Brevilin A targets. Lung cancer-related targets were sourced from GEO, Genecards, OMIM, TTD, and Drugbank databases. Utilizing Cytoscape software, a protein-protein interaction (PPI) network was established. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene set enrichment analysis (GSEA), and gene-pathway correlation analysis were conducted using R software. To validate network pharmacology results, molecular docking, molecular dynamics simulations, and in vitro experiments were performed. We identified 599 Brevilin A-associated targets and 3864 lung cancer-related targets, with 155 overlapping genes considered as candidate targets for Brevilin A against lung cancer. The PPI network highlighted STAT3, TNF, HIF1A, PTEN, ESR1, and MTOR as potential therapeutic targets. GO and KEGG analyses revealed 2893 enriched GO terms and 157 enriched KEGG pathways, including the PI3K-Akt signaling pathway, FoxO signaling pathway, and HIF-1 signaling pathway. GSEA demonstrated a close association between hub genes and lung cancer. Gene-pathway correlation analysis indicated significant associations between hub genes and the cellular response to hypoxia pathway. Molecular docking and dynamics simulations confirmed Brevilin A’s interaction with PTEN and HIF1A, respectively. In vitro experiments demonstrated Brevilin A-induced dose- and time-dependent cell death in A549 cells. Notably, Brevilin A treatment significantly reduced HIF-1α mRNA expression while increasing PTEN mRNA levels. This study demonstrates that Brevilin A exerts anti-cancer effects in treating lung cancer through a multi-target and multi-pathway manner, with the HIF pathway potentially being involved. These results lay a theoretical foundation for the prospective clinical application of Brevilin A.
传统中医药在肿瘤治疗中得到了广泛应用,并产生了前景广阔的候选疗法。先前的研究揭示了从中草药蜈蚣(Centipeda minima (L.) A.Br.)(C. minima)中提取的天然倍半萜内酯 Brevilin A 的抗癌特性,尤其是对肺癌的抗癌特性。然而,其作用的潜在机制仍然难以捉摸。本研究采用网络药理学和实验分析方法来揭示百脉通 A 在肺癌中的分子机制。研究人员筛选了 Batman-TCM、Swiss Target Prediction、Pharmmapper、SuperPred 和 BindingDB 数据库,以确定 Brevilin A 靶点。肺癌相关靶点来自 GEO、Genecards、OMIM、TTD 和 Drugbank 数据库。利用 Cytoscape 软件建立了蛋白质-蛋白质相互作用(PPI)网络。利用 R 软件进行了基因本体(GO)、京都基因和基因组百科全书(KEGG)、基因组富集分析(GSEA)和基因通路相关性分析。为了验证网络药理学结果,我们进行了分子对接、分子动力学模拟和体外实验。我们发现了599个Brevilin A相关靶点和3864个肺癌相关靶点,其中155个重叠基因被认为是Brevilin A抗肺癌的候选靶点。PPI网络强调STAT3、TNF、HIF1A、PTEN、ESR1和MTOR是潜在的治疗靶点。GO和KEGG分析显示了2893个富集的GO术语和157个富集的KEGG通路,包括PI3K-Akt信号通路、FoxO信号通路和HIF-1信号通路。GSEA显示了枢纽基因与肺癌之间的密切联系。基因通路相关性分析表明,中心基因与细胞对缺氧的反应通路之间存在显著关联。分子对接和动力学模拟分别证实了 Brevilin A 与 PTEN 和 HIF1A 的相互作用。体外实验证明,Brevilin A 可诱导 A549 细胞发生剂量和时间依赖性细胞死亡。值得注意的是,Brevilin A 处理可显著降低 HIF-1α mRNA 表达,同时提高 PTEN mRNA 水平。这项研究表明,Brevilin A 通过多靶点、多途径的方式发挥治疗肺癌的抗癌作用,HIF 途径可能参与其中。这些结果为 Brevilin A 的临床应用前景奠定了理论基础。
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引用次数: 0
Correction: Centipeda minima active components and mechanisms in lung cancer 更正:蜈蚣小体的活性成分及其在肺癌中的作用机制
2区 医学 Q1 Medicine Pub Date : 2024-05-15 DOI: 10.1186/s12906-024-04498-y
Cuiyun Gao, Huafeng Pan, Fengjun Ma, Ze Zhang, Zedan Zhao, Jialing Song, Wei Li, Xiangzhen Fan

Correction: BMC Complement Med Ther (2023) 23:89

https://doi.org/10.1186/s12906-023-03915-y

Following publication of the original article [1], the authors reported an error in in the grant number for the first fund provided in the paper.

The correct grant number should be “No. ZR2022QH001”, instead of “No. ZR202111290609”.

The original article has been corrected.

  1. Gao C, Pan H, Ma F, et al. Centipeda minima active components and mechanisms in lung cancer. BMC Complement Med Ther. 2023;23:89. https://doi.org/10.1186/s12906-023-03915-y.

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  1. Cuiyun Gao and Huafeng Pan are co-first author.

Authors and Affiliations

  1. Department of Rehabilitation Medicine, Binzhou Medical University Hospital, Binzhou, Shandong, China

    Cuiyun Gao, Wei Li & Xiangzhen Fan

  2. School of Rehabilitation Medicine, Binzhou Medical University, Yantai, Shandong, China

    Cuiyun Gao, Ze Zhang, Zedan Zhao & Jialing Song

  3. Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China

    Huafeng Pan

  4. Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China

    Fengjun Ma

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更正:BMC Complement Med Ther (2023) 23:89https://doi.org/10.1186/s12906-023-03915-yFollowing 发表原文[1]时,作者报告论文中提供的第一笔基金的基金号有误。正确的基金号应为 "No.ZR2022QH001",而不是 "No.ZR202111290609"。原文已更正。Gao C, Pan H, Ma F, et al. Centipeda minima active components and mechanisms in lung cancer.BMC Complement Med Ther.https://doi.org/10.1186/s12906-023-03915-y.Article CAS PubMed PubMed Central Google Scholar 下载参考文献作者简介高翠云和潘华峰为共同第一作者。作者及单位滨州医科大学附属医院康复医学科,山东滨州Cuiyun Gao, Wei Li & Xiangzhen Fan滨州医科大学康复医学院,山东烟台Cuiyun Gao, Ze Zhang, Zedan Zhao &;宋嘉陵广州中医药大学科技创新中心,广东广州潘华锋山东中医药大学,山东济南、发表文章您也可以在PubMed Google Scholar中搜索该作者宋嘉陵查看作者发表文章您也可以在PubMed Google Scholar中搜索该作者李伟查看作者发表文章您也可以在PubMed Google Scholar中搜索该作者范向真查看作者发表文章您也可以在PubMed Google Scholar中搜索该作者通讯作者:李伟或范向真。出版者注Springer Nature对已出版地图中的管辖权主张和机构隶属关系保持中立。原文的在线版本可在以下网址找到:https://doi.org/10.1186/s12906-023-03915-y.Open Access 本文采用知识共享署名 4.0 国际许可协议进行许可,该协议允许以任何媒介或格式使用、共享、改编、分发和复制,只要您适当注明原作者和来源,提供知识共享许可协议的链接,并说明是否进行了修改。本文中的图片或其他第三方材料均包含在文章的知识共享许可协议中,除非在材料的署名栏中另有说明。如果材料未包含在文章的知识共享许可协议中,且您打算使用的材料不符合法律规定或超出许可使用范围,您需要直接从版权所有者处获得许可。要查看该许可的副本,请访问 http://creativecommons.org/licenses/by/4.0/。除非在数据的信用行中另有说明,否则知识共享公共领域专用免责声明 (http://creativecommons.org/publicdomain/zero/1.0/) 适用于本文提供的数据。转载与许可引用本文Gao, C., Pan, H., Ma, F. et al. Correction:蜈蚣的活性成分及在肺癌中的作用机制。BMC Complement Med Ther 24, 191 (2024). https://doi.org/10.1186/s12906-024-04498-yDownload citationPublished: 15 May 2024DOI: https://doi.org/10.1186/s12906-024-04498-yShare this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative.
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引用次数: 0
Bawei Chenxiang Wan ameliorates right ventricular hypertrophy in rats with high altitude heart disease by SIRT3-HIF1α-PDK/PDH signaling pathway improving fatty acid and glucose metabolism 八味沉香丸通过SIRT3-HIF1α-PDK/PDH信号通路改善脂肪酸和葡萄糖代谢,从而改善高海拔心脏病大鼠的右心室肥厚
2区 医学 Q1 Medicine Pub Date : 2024-05-15 DOI: 10.1186/s12906-024-04490-6
Yiwei Han, Shadi Li, Zhiying Zhang, Xin Ning, Jiajia Wu, Xiaoying Zhang
Bawei Chenxiang Wan (BCW) is among the most effective and widely used therapies for coronary heart disease and angina pectoris in Tibet. However, whether it confers protection through a right-ventricle (RV) myocardial metabolic mechanism is unknown. Male Sprague–Dawley rats were orally administrated with BCW, which was injected concurrently with a bolus of Sugen5416, and subjected to hypoxia exposure (SuHx; 5000 m altitude) for 4 weeks. Right ventricular hypertrophy (RVH) in high-altitude heart disease (HAHD) was assessed using Fulton’s index (FI; ratio of RV to left ventricle + septum weights) and heart-weight-to-body-weight ratio (HW/BW). The effect of therapeutic administration of BCW on the RVH hemodynamics was assessed through catheterization (mean right ventricular pressure and mean pulmonary artery pressure (mRVP and mPAP, respectively)). Tissue samples were used to perform histological staining, and confirmatory analyses of mRNA and protein levels were conducted to detect alterations in the mechanisms of RVH in HAHD. The protective mechanism of BCW was further verified via cell culture. BCW considerably reduced SuHx-associated RVH, as indicated by macro morphology, HW/BW ratio, FI, mPAP, mRVP, hypertrophy markers, heart function, pathological structure, and myocardial enzymes. Moreover, BCW can alleviate the disorder of glucose and fatty acid metabolism through upregulation of carnitine palmitoyltransferase1ɑ, citrate synthase, and acetyl-CoA and downregulation of glucose transport-4, phosphofructokinase, and pyruvate, which resulted in the reduced levels of free fatty acid and lactic acid and increased aerobic oxidation. This process may be mediated via the regulation of sirtuin 3 (SIRT3)-hypoxia-inducible factor 1α (HIF1α)-pyruvate dehydrogenase kinase (PDK)/pyruvate dehydrogenase (PDH) signaling pathway. Subsequently, the inhibition of SIRT3 expression by 3-TYP (a selective inhibitor of SIRT3) can reverse substantially the anti-RVH effect of BCW in HAHD, as indicated by hypertrophy marker and serum myocardial enzyme levels. BCW prevented SuHx-induced RVH in HAHD via the SIRT3-HIF1ɑ-PDK/PDH signaling pathway to alleviate the disturbance in fatty acid and glucose metabolism. Therefore, BCW can be used as an alternative drug for the treatment of RVH in HAHD.
八味陈香丸(BCW)是西藏治疗冠心病和心绞痛最有效和最广泛使用的疗法之一。然而,它是否通过右心室心肌代谢机制提供保护尚不清楚。雄性 Sprague-Dawley 大鼠在口服 BCW 的同时注射 Sugen5416,并接受为期 4 周的缺氧暴露(SuHx;海拔 5000 米)。高海拔心脏病(HAHD)中的右心室肥大(RVH)是通过富尔顿指数(FI;RV与左心室+室间隔重量之比)和心脏重量/体重比(HW/BW)进行评估的。通过导管检查(平均右心室压和平均肺动脉压(分别为 mRVP 和 mPAP))评估了治疗性服用 BCW 对 RVH 血液动力学的影响。采用组织样本进行组织学染色,并对 mRNA 和蛋白质水平进行确证分析,以检测 HAHD 患者 RVH 机制的改变。BCW 的保护机制通过细胞培养得到了进一步验证。从宏观形态、HW/BW比值、FI、mPAP、mRVP、肥厚标志物、心脏功能、病理结构和心肌酶等方面来看,BCW大大降低了SuHx相关的RVH。此外,BCW 还能通过上调肉碱棕榈酰基转移酶 1ɑ、柠檬酸合成酶和乙酰-CoA,下调葡萄糖转运-4、磷酸果糖激酶和丙酮酸,缓解葡萄糖和脂肪酸代谢紊乱,从而降低游离脂肪酸和乳酸水平,增加有氧氧化。这一过程可能是通过调节sirtuin 3(SIRT3)-缺氧诱导因子1α(HIF1α)-丙酮酸脱氢酶激酶(PDK)/丙酮酸脱氢酶(PDH)信号通路介导的。随后,3-TYP(SIRT3的一种选择性抑制剂)抑制SIRT3的表达,可从肥厚标志物和血清心肌酶水平上显著逆转BCW对HAHD的抗RVH作用。BCW通过SIRT3-HIF1ɑ-PDK/PDH信号通路防止SuHx诱导的HAHD RVH,从而缓解脂肪酸和葡萄糖代谢紊乱。因此,BCW可作为治疗HAHD RVH的替代药物。
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引用次数: 0
Wine- and stir-frying processing of Cuscutae Semen enhance its ability to alleviate oxidative stress and apoptosis via the Keap 1-Nrf2/HO-1 and PI3K/AKT pathways in H2O2-challenged KGN human granulosa cell line 酒炒菟丝子精液可通过Keap 1-Nrf2/HO-1和PI3K/AKT途径缓解H2O2挑战下KGN人颗粒细胞系的氧化应激和细胞凋亡
2区 医学 Q1 Medicine Pub Date : 2024-05-15 DOI: 10.1186/s12906-024-04491-5
Yusha Liang, Yun Shi, Rong Guo, Changli Xu, Mian Fu, Jinyang Shen, Xun Gao, Weidong Li, Kunming Qin
Cuscutae Semen (CS) has been prescribed in traditional Chinese medicine (TCM) for millennia as an aging inhibitor, an anti-inflammatory agent, a pain reliever, and an aphrodisiac. Its three main forms include crude Cuscutae Semen (CCS), wine-processed CS (WCS), and stir-frying-processed CS (SFCS). Premature ovarian insufficiency (POI) is a globally occurring medical condition. The present work sought a highly efficacious multi-target therapeutic approach against POI with minimal side effects. Finally, it analyzed the relative differences among CCS, WCS and SFCS in terms of their therapeutic efficacy and modes of action against H2O2-challenged KGN human granulosa cell line. In this study, ultrahigh-performance liquid chromatography (UPLC)-Q-ExactiveTM Orbitrap-mass spectrometry (MS), oxidative stress indices, reactive oxygen species (ROS), Mitochondrial membrane potential (MMP), real-time PCR, Western blotting, and molecular docking were used to investigate the protective effect of CCS, WCS and SFCS on KGN cells oxidative stress and apoptosis mechanisms. The results confirmed that pretreatment with CCS, WCS and SFCS reduced H2O2-induced oxidative damage, accompanied by declining ROS levels and malondialdehyde (MDA) accumulation in the KGN cells. CCS, WCS and SFCS upregulated the expression of antioxidative levels (GSH, GSH/GSSG ratio, SOD, T-AOC),mitochondrial membrane potential (MMP) and the relative mRNA(Nrf2, Keap1, NQO-1, HO-1, SOD-1, CAT). They inhibited apoptosis by upregulating Bcl-2, downregulating Bax, cleaved caspase-9, and cleaved caspase-3, and lowering the Bax/Bcl-2 ratio. They also exerted antioxidant efficacy by partially activating the PI3K/Akt and Keap1-Nrf2/HO-1 signaling pathways. The results of the present work demonstrated the inhibitory efficacy of CCS, WCS and SFCS against H2O2-induced oxidative stress and apoptosis in KGN cells and showed that the associated mechanisms included Keap1-Nrf2/HO-1 activation, P-PI3K upregulation, and P-Akt-mediated PI3K-Akt pathway induction.
千百年来,菟丝子精液(Cuscutae Semen,CS)一直是传统中医(TCM)的处方药,具有抗衰老、消炎、止痛和壮阳的作用。其三种主要形式包括粗制菟丝子精液(CCS)、酒制菟丝子精液(WCS)和炒制菟丝子精液(SFCS)。卵巢早衰(POI)是一种全球性的疾病。本研究寻求一种副作用最小的高效多靶点治疗方法来治疗早发性卵巢功能不全。最后,本研究分析了 CCS、WCS 和 SFCS 对 H2O2 挑战的 KGN 人类颗粒细胞系的疗效和作用模式的相对差异。本研究采用超高效液相色谱(UPLC)-Q-ExactiveTM Orbitrap-质谱(MS)、氧化应激指数、活性氧(ROS)、线粒体膜电位(MMP)、实时 PCR、Western 印迹和分子对接等方法研究了 CCS、WCS 和 SFCS 对 KGN 细胞氧化应激和细胞凋亡机制的保护作用。结果证实,使用 CCS、WCS 和 SFCS 预处理可减少 H2O2 诱导的氧化损伤,同时降低 KGN 细胞中的 ROS 水平和丙二醛(MDA)积累。CCS、WCS 和 SFCS 提高了抗氧化水平(GSH、GSH/GSSG 比值、SOD、T-AOC)、线粒体膜电位(MMP)和相对 mRNA(Nrf2、Keap1、NQO-1、HO-1、SOD-1、CAT)的表达。它们通过上调 Bcl-2、下调 Bax、裂解的 caspase-9 和裂解的 caspase-3 以及降低 Bax/Bcl-2 比率来抑制细胞凋亡。它们还通过部分激活 PI3K/Akt 和 Keap1-Nrf2/HO-1 信号通路发挥抗氧化功效。本研究结果表明,CCS、WCS和SFCS对H2O2诱导的KGN细胞氧化应激和凋亡具有抑制作用,相关机制包括Keap1-Nrf2/HO-1激活、P-PI3K上调和P-Akt介导的PI3K-Akt通路诱导。
{"title":"Wine- and stir-frying processing of Cuscutae Semen enhance its ability to alleviate oxidative stress and apoptosis via the Keap 1-Nrf2/HO-1 and PI3K/AKT pathways in H2O2-challenged KGN human granulosa cell line","authors":"Yusha Liang, Yun Shi, Rong Guo, Changli Xu, Mian Fu, Jinyang Shen, Xun Gao, Weidong Li, Kunming Qin","doi":"10.1186/s12906-024-04491-5","DOIUrl":"https://doi.org/10.1186/s12906-024-04491-5","url":null,"abstract":"Cuscutae Semen (CS) has been prescribed in traditional Chinese medicine (TCM) for millennia as an aging inhibitor, an anti-inflammatory agent, a pain reliever, and an aphrodisiac. Its three main forms include crude Cuscutae Semen (CCS), wine-processed CS (WCS), and stir-frying-processed CS (SFCS). Premature ovarian insufficiency (POI) is a globally occurring medical condition. The present work sought a highly efficacious multi-target therapeutic approach against POI with minimal side effects. Finally, it analyzed the relative differences among CCS, WCS and SFCS in terms of their therapeutic efficacy and modes of action against H2O2-challenged KGN human granulosa cell line. In this study, ultrahigh-performance liquid chromatography (UPLC)-Q-ExactiveTM Orbitrap-mass spectrometry (MS), oxidative stress indices, reactive oxygen species (ROS), Mitochondrial membrane potential (MMP), real-time PCR, Western blotting, and molecular docking were used to investigate the protective effect of CCS, WCS and SFCS on KGN cells oxidative stress and apoptosis mechanisms. The results confirmed that pretreatment with CCS, WCS and SFCS reduced H2O2-induced oxidative damage, accompanied by declining ROS levels and malondialdehyde (MDA) accumulation in the KGN cells. CCS, WCS and SFCS upregulated the expression of antioxidative levels (GSH, GSH/GSSG ratio, SOD, T-AOC),mitochondrial membrane potential (MMP) and the relative mRNA(Nrf2, Keap1, NQO-1, HO-1, SOD-1, CAT). They inhibited apoptosis by upregulating Bcl-2, downregulating Bax, cleaved caspase-9, and cleaved caspase-3, and lowering the Bax/Bcl-2 ratio. They also exerted antioxidant efficacy by partially activating the PI3K/Akt and Keap1-Nrf2/HO-1 signaling pathways. The results of the present work demonstrated the inhibitory efficacy of CCS, WCS and SFCS against H2O2-induced oxidative stress and apoptosis in KGN cells and showed that the associated mechanisms included Keap1-Nrf2/HO-1 activation, P-PI3K upregulation, and P-Akt-mediated PI3K-Akt pathway induction.","PeriodicalId":9132,"journal":{"name":"BMC Complementary and Alternative Medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140940598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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BMC Complementary and Alternative Medicine
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